Inhibition of microRNA-122 alleviates pyroptosis by targeting dual-specificity phosphatase 4 in myocardial ischemia/reperfusion injury

Pyroptosis is a type of programmed cell death that induces myocardial ischemia-reperfusion injury (I/RI), which leads to cardiac dysfunction and even lethal reperfusion injury. MiR-122 is a liver-specific miRNA associated with coronary heart disease, but its role in pyroptosis activation in myocardial I/RI remains unclear. Thus, this study aimed to determine whether miR-122 inhibition exerts myocardial I/RI protection in in vivo and in vitro models. An I/RI model was established in vivo using C57BL/J6 male mice. MiR-122 expression was upregulated in the heart tissues from the I/RI group. Quantitative results of echocardiography parameters showed that miR-122 inhibition improved cardiac function and downregulated interleukin (IL)-1β, IL-18, caspase 1, and caspase 11. However, pretransfection with recombinant adeno-associated virus type 9 encoding a DUSP4-specific siRNA (AAV9-siDUSP4) blocked the protective effects of miR-122 inhibition. A hypoxia/reoxygenation (H/R) model was established to mimic the I/R condition in vitro using H9C2 cells. Results showed that miR-122 inhibition increased superoxide dismutase activity (SOD) and cell viability and decreased malondialdehyde (MDA) level, IL-1β, IL-18, caspase 1, caspase 11, and cell death. These protective effects were abolished by transfection with DUSP4-specific siRNA. In summary, miR-122 expression is upregulated in I/RI, and miR-122 inhibition alleviates I/RI by suppressing pyroptosis through targeting DUSP4. Thus, miR-122 may be a novel therapeutic target for treating myocardial I/RI.